Adjuvants are vaccine components that enhance the magnitude, breadth and durability of the immune response. Following its introduction in the 1920s, alum remained the only adjuvant licensed for human use for the next 70 years. Since the 1990s, a further five adjuvants have been included in licensed vaccines, but the molecular mechanisms by which these adjuvants work remain only partially understood. However, a revolution in our understanding of the activation of the innate immune system through pattern recognition receptors (PRRs) is improving the mechanistic understanding of adjuvants, and recent conceptual advances highlight the notion that tissue damage, different forms of cell death, and metabolic and nutrient sensors can all modulate the innate immune system to activate adaptive immunity. Furthermore, recent advances in the use of systems biology to probe the molecular networks driving immune response to vaccines ('systems vaccinology') are revealing mechanistic insights and providing a new paradigm for the vaccine discovery and development process. Here, we review the 'known knowns' and 'known unknowns' of adjuvants, discuss these emerging concepts and highlight how our expanding knowledge about innate immunity and systems vaccinology are revitalizing the science and development of novel adjuvants for use in vaccines against COVID-19 and future pandemics.

/pdf/emerging-concepts-in-the-science-of-vaccine-adjuvants-2mbz7det2l.pdf

Emerging concepts in the science of vaccine adjuvants.

17 – Inactivated influenza vaccines

Side effects and perceptions following Sinopharm COVID-19 vaccination.

Consensus summary report for CEPI/BC March 12-13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines.

Can a COVID-19 vaccine live up to Americans' expectations? A conjoint analysis of how vaccine characteristics influence vaccination intentions.

Reactogenicity represents the physical manifestation of the inflammatory response to vaccination, and can include injection-site pain, redness, swelling or induration at the injection site, as well as systemic symptoms, such as fever, myalgia, or headache. The experience of symptoms following vaccination can lead to needle fear, long-term negative attitudes and non-compliant behaviours, which undermine the public health impact of vaccination. This review presents current knowledge on the potential causes of reactogenicity, and how host characteristics, vaccine administration and composition factors can influence the development and perception of reactogenicity. The intent is to provide an overview of reactogenicity after vaccination to help the vaccine community, including healthcare professionals, in maintaining confidence in vaccines by promoting vaccination, setting expectations for vaccinees about what might occur after vaccination and reducing anxiety by managing the vaccination setting.

/pdf/the-how-s-and-what-s-of-vaccine-reactogenicity-2qm46h81bm.pdf

The how’s and what’s of vaccine reactogenicity

Adjuvant Systems for vaccines: 13 years of post-licensure experience in diverse populations have progressed the way adjuvanted vaccine safety is investigated and understood.

The effectiveness of trivalent influenza vaccines may be reduced in older versus younger adults because of age-related immunosenescence. The use of an adjuvant in such a vaccine is one strategy that may combat immunosenescence, potentially by bolstering T-cell mediated responses. This observer-blind study, conducted in the United States (US) and Spain during the 2008–2009 influenza season, evaluated the effect of Adjuvant System AS03 on specific T-cell responses to a seasonal trivalent influenza vaccine (TIV) in ≥65 year-old adults. Medically-stable adults aged ≥65 years were randomly allocated to receive a single dose of AS03-adjuvanted TIV (TIV/AS03) or TIV. Healthy adults aged 18–40 years received only TIV. Blood samples were collected on Day 0, Day 21, Day 42 and Day 180. Influenza-specific CD4+ T cells, defined by the induction of the immune markers CD40L, IL-2, IFN-γ, or TNF-α, were measured in ex vivo cultures of antigen-stimulated peripheral blood mononuclear cells. A total of 192 adults were vaccinated: sixty nine and seventy three ≥65 year olds received TIV/AS03 and TIV, respectively; and fifty 18 - 40 year olds received TIV. In the ≥65 year-old group on Day 21, the frequency of CD4+ T cells specific to the three vaccine strains was superior in the TIV/AS03 recipients to the frequency in TIV (p < 0.001). On Days 42 and 180, the adjusted-geometric mean specific CD4+ T-cell frequencies were also higher in the TIV/AS03 recipients than in the TIV recipients (p < 0.001). Furthermore, the adjusted-geometric mean specific CD4+ T-cell frequencies were higher in the ≥65 year-old recipients of TIV/AS03 than in the18 - 40 year old recipients of TIV on Days 21 (p = 0.006) and 42 (p = 0.011). This positive effect of AS03 Adjuvant System on the CD4+ T-cell response to influenza vaccine strains in older adults could confer benefit in protection against clinical influenza disease in this population. (Clinicaltrials.gov.). NCT00765076
 .

http://diposit.ub.edu/dspace/bitstream/2445/68435/1/couch2014_1799.pdf

Superior antigen-specific CD4+T-cell response with AS03-adjuvantation of a trivalent influenza vaccine in a randomised trial of adults aged 65 and older

The primary goal of vaccination is the prevention of pathogen-specific infection. The indirect consequences may include maintenance of homeostasis through prevention of infection-induced complications; trained immunity that re-programs innate cells to respond more efficiently to later, unrelated threats; slowing or reversing immune senescence by altering the epigenetic clock, and leveraging the pool of memory B and T cells to improve responses to new infections. Vaccines may exploit the plasticity of the immune system to drive longer-term immune responses that promote health at a broader level than just the prevention of single, specific infections. In this perspective, we discuss the concept of “immune fitness” and how to potentially build a resilient immune system that could contribute to better health. We argue that vaccines may contribute positively to immune fitness in ways that are only beginning to be understood, and that life-course vaccination is a fundamental tool for achieving healthy aging.

/pdf/vaccination-as-a-preventative-measure-contributing-to-immune-3vx2ydmil4.pdf

Vaccination as a preventative measure contributing to immune fitness.

Vaccine development has traditionally been driven by the need to prevent high numbers of childhood deaths due to infectious disease. With few exceptions, vaccines for adults are the same as vaccines for infants, although it has long been apparent that they become less effective as age increases. It is only in the last few years that concerted efforts have commenced to develop life-long vaccination strategies through into older age. Impressive progress has been made in the field of vaccine technologies which, when they will be applied to vaccination of older adults, could change the landscape for disease prevention in this age group. The recently licensed adjuvanted herpes zoster vaccine shows that immunosenescence need not be a barrier to highly effective vaccination, and that highly effective vaccines for older adults can be achieved with good vaccine design. One of the greatest public health challenges of the 21st century is ensuring the health and well-being of the aged. New or improved vaccines targeting pathogens with a high disease burden in older adults have the potential to major contributions to the longevity and productivity of the older aged population.

Béatrice Laupèze

Papers

The how’s and what’s of vaccine reactogenicity

Adjuvant Systems for vaccines: 13 years of post-licensure experience in diverse populations have progressed the way adjuvanted vaccine safety is investigated and understood.

Superior antigen-specific CD4+T-cell response with AS03-adjuvantation of a trivalent influenza vaccine in a randomised trial of adults aged 65 and older

Vaccination as a preventative measure contributing to immune fitness.

Novel Technologies to Improve Vaccines for Older Adults.